Negative modulation of suppressive HIV-specific regulatory T cells by IL-2 adjuvanted therapeutic vaccine Vedran Brezar Lylia Hani Mathieu Surenaud Audrey Hubert Christine Lacabaratz Jean-Daniel Lelièvre Yves Levy Nabila Seddiki 10.1371/journal.ppat.1006489 https://plos.figshare.com/articles/dataset/Negative_modulation_of_suppressive_HIV-specific_regulatory_T_cells_by_IL-2_adjuvanted_therapeutic_vaccine/5211145 <div><p>The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40. IL-2 administration increased significantly HIV-specific CD4<sup>+</sup>CD25<sup>+</sup>CD134<sup>+</sup> T-cell responses, which inversely correlated with viral load after TI (r = -0.7, p <0.007) in the vaccine/IL-2 group. IL-2 increased global CD25<sup>+</sup>CD127<sup>low</sup>FoxP3<sup>+</sup>Tregs (p <0.05) while it decreased HIV- but not CMV- specific CD39<sup>+</sup>FoxP3<sup>+</sup>CD25<sup>+</sup>CD134<sup>+</sup>Tregs (p <0.05). HIV-specific Tregs were inversely correlated with IFN-γ producing specific-effectors (p = 0.03) and positively correlated with viral load (r = 0.7, p = 0.01), revealing their undesired presence during chronic infection. Global Tregs, but not HIV-specific Tregs, inversely correlated with a decrease in exhausted PD1<sup>+</sup>CD95<sup>+</sup> T-cells (p = 0.001). Altogether, our results underline the negative impact of HIV-specific Tregs on HIV-specific effectors and reveal the beneficial use of IL-2 as an adjuvant as its administration increases global Tregs that impact on T-cell exhaustion and decreases HIV-specific CD39<sup>+</sup>Tregs by shifting the balance towards effectors.</p></div> 2017-07-14 09:09:26 HIV-specific Tregs HIV-specific CD 4 Antiretroviral therapy treated-patients week 40. IL -2 administration decreases HIV-specific CD 39 CD 25 FoxP 3 ALVACHIV CMV IFN IL -2 CD 134 PD IL -2 adjuvanted TI